title: Rhinovirus-induced calcium flux triggers NLRP3 and NLRC5 activation in bronchial cells.
abstract: Human rhinoviruses have been linked with underlying lung disorders, such as asthma and chronic obstructive pulmonary disease, in children and adults. However, the mechanism of virus-induced airway inflammation is poorly understood. In this study, using virus deletion mutants and silencing for nucleotide-binding oligomerization domain-like receptors (NLRs), we show that the rhinovirus ion channel protein 2B triggers NLRP3 and NLRC5 inflammasome activation and IL-1β secretion in bronchial cells. 2B protein targets the endoplasmic reticulum and Golgi and induces Ca(2+) reduction in these organelles, thereby disturbing the intracellular calcium homeostasis. NLRP3 and NLRC5 act in a cooperative manner during the inflammasome assembly by sensing intracellular Ca(2+) fluxes and trigger IL-1β secretion. These results reveal for the first time that human rhinovirus infection in primary bronchial cells triggers inflammasome activation.
authors.affiliation: 1 Cardiff University, Institute of Infection and Immunity, Department of Child Health, School of Medicine, University Hospital of Wales, Heath Park, Cardiff, Wales; and.
authors.forename: Kathy
authors.initials: K
authors.lastname: Triantafilou
authors.forename: Satwik
authors.initials: S
authors.lastname: Kar
authors.forename: Frank J M
authors.initials: FJ
authors.lastname: van Kuppeveld
authors.forename: Martha
authors.initials: M
authors.lastname: Triantafilou
mesh_terms: D001249:Asthma / Q000209:etiology / Q000378:metabolism / Q000821:virology; D001980:Bronchi / Q000378:metabolism* / Q000821:virology*; D020013:Calcium Signaling / Q000502:physiology*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000821:virology; D055785:Gene Knockdown Techniques; D006056:Golgi Apparatus / Q000378:metabolism / Q000821:virology; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D053583:Interleukin-1beta / Q000096:biosynthesis; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010850:Picornaviridae Infections / Q000150:complications / Q000378:metabolism / Q000821:virology; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology / Q000378:metabolism / Q000821:virology; D012229:Rhinovirus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D047908:Intracellular Signaling Peptides and Proteins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C548042:NLRC5 protein, human; C453881:NLRP3 protein, human; D014764:Viral Proteins